CENTER OVERVIEW ? ABSTRACT For 30 years, the Diabetes Research Center (DRC) of the Joslin Diabetes Center, with its core laboratories including the Boston University-Joslin Regional Computational core (BUJRC), Enrichment Program, and Pilot and Feasibility (P&F) program, has synergized the collaborative expansion of basic and clinical diabetes research at Joslin, Harvard Medical School (HMS) and the neighboring research institutions. During the last 5 years, the Joslin Research Division generated paradigm-changing breakthroughs on the understanding of the pathogenesis of various forms of diabetes and its complications. The success in making these discoveries has been closely linked to the continuously evolving technologies and computational biology services provided by the Joslin DRC. In addition, Joslin made significant renovations to many of its clinical and research laboratories. This application summarizes the progress and innovations that have been made to the various components of the Joslin DRC over this grant period. The Animal Physiology Core and Flow Cytometry Core will have exciting new capabilities with the building of a germ-free mouse facility and the acquisition of new cell sorting and imaging instruments. The Advanced Genomic and Genetics Core will become the Molecular Phenotyping and Genotyping Core, allowing the incorporation of bioenergetics and new DNA chip capabilities. The iPS Cell Core will be Genome Editing Core, introducing CRISPR-Cas9 technology for cell-based and rodent model studies. The BUJRC Bioinformatics Core, due to significant increase in demand, will be enlarged to add new services. The DRC is also proposing a new Clinical Translational Research Center Core (CTRC), which will complement our renovated and enlarged Clinical Research Center facility that is funded by Joslin. The CTRC is being proposed due to the significant increase in our translational and clinical research studies, which now account for 50% of Joslin's research efforts. This new Core will coordinate and synergize the large number of clinical/translational studies now on-going at Joslin and enhance their capabilities by improving clinical design, specific procedures for metabolic studies, identification of special diabetic populations and cohorts, and facilitating sources and resources for biological samples and repositories. The previously DRC-supported Advanced Microscopy Core, the Animal Facilities, Specialized Assay Core, Media Core and the Clinical Research Center will continue with support by Joslin. The P&F program has been very successful in supporting early investigators, thus identifying innovative research at Joslin, Harvard and Boston institutions. More than half of P+F Program awardees have subsequently competed successfully for NIH support. The Enrichment Program is the largest diabetes and metabolic disease educational program for post-doctoral fellows, students and investigators in the Harvard Medical School area, and is jointly supported by the DRC and Joslin funding. Joslin hosts a large international symposium every three years. Thus, the role of the DRC has been clearly important to this community of investigators and will continue to be pivotal in the proposed grant period.